COMPARISON STUDIES SHOWING SWELLING EFFECT AND DRUG RELEASE PATTERN FROM MATRICES CONTAINING DIFFERENT DRUGS AND SAME POLYMER COMBINATIONS

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www.wjpr.net Vol 6, Issue 14, 2017. 1192

COMPARISON STUDIES SHOWING SWELLING EFFECT AND DRUG

RELEASE PATTERN FROM MATRICES CONTAINING DIFFERENT

DRUGS AND SAME POLYMER COMBINATIONS

Masheer Ahmed Khan*

School of Pharmacy, Devi Ahilya Vishwavidyalaya, Takshshila Campus, Khandwa Road,

Indore, 452001, India.

ABSTRACT

Polymers are excellent drug carriers and widely used in the

formulation of matrices to prolong the release of drug from the

devices. The present comparison studies shows swelling effect and

drug release pattern from matrices of Atenolol and Diltiazem

hydrochloride drugs containing same polymer combinations. Matrices

of both the drugs are prepared using same grades of hydroxypropyl

methylcellulose (HPMC), viz, HPMCK4M, HPMCK15M and

HPMCK100M. The study examines the degree of swelling and percent

water uptake for matrices containing same polymer concentrations and

combinations. The results indicate that swelling and release profiles

were affected by concentration and viscosity grades of the polymer.

The higher amount of polymer causes a greater degree of swelling this in turn reduces the

drug release, as the diffusional path length of drug is longer and conversely, reduction in the

amount of polymer reduces the degree of swelling and the thickness of gel layer, this enables

faster drug release. Swelling studies reveals an inverse relationship between swelling effect

and drug release pattern from both the drugs matrices using the same polymer combinations.

Comparison studies shows almost similar swelling effect and drug release pattern from

matrices containing different drugs and same polymer combinations.

KEYWORDS: Polymer, Swelling, Matrices, Drug release.

INTRODUCTION

The aim of the present study was to compare swelling effect and drug release pattern from the

matrices of atenolol and diltiazem hydrochloride prepared using same grades of

Volume 6, Issue 14, 1192-1201. Research Article ISSN 2277– 7105

Article Received on 20 September 2017,

Revised on 11 October 2017, Accepted on 01 Nov. 2017

DOI: 10.20959/wjpr201714-10064

8533

*Corresponding Author

Masheer Ahmed Khan

School of Pharmacy, Devi

Ahilya Vishwavidyalaya,

Takshshila Campus,

Khandwa Road, Indore,

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hydroxypropyl methylcellulose (HPMC), viz, HPMCK4M, HPMCK15M and HPMCK100M.

Sustained release drug delivery system is designed to achieve a prolonged therapeutic effect

by continuously releasing medication over an extended period of time after administration of

a single dose. Hydrophilic matrices devices are one of the least complicated approaches in the

formulation of sustained release dosage forms and are finding increasing application in the

pharmaceutical field.[1-6]

Drug release data from HPMC matrices for both the drugs follows the classical Higuchi

dissolution equation, relating drug release with square root of time. Swellable systems

consisting of hydrophilic polymers, in the presence of water, absorb a significant amount of

water to form a gel. As the dissolution medium penetrates the matrix, polymer material

swelling starts and drug molecules begin to move out of the system by diffusion. The degree

of swelling and percent water uptake is determined to find the relationship between the drug

release and swelling. The release mechanism is obtained from the dissolution data and the

value of release rate exponent is determined. The value of release rate exponent (n) is a

function of geometric shape of the drug delivery device. The release is mainly determined by

the Fickian diffusion which is also confirmed from the n values.[7-12]

EXPERIMENTAL

MATERIALS AND METHODS

Atenolol and Diltiazem hydrochloride were obtained as a gift sample from Pure Pharma.

Labs Ltd, Indore, (M.P.), HPMC (K4M, K15M, K100M) were provided by Colorcon

India Ltd., Goa, dicalcium phosphate, microcrystalline cellulose (Avicel), talc , magnesium

stearate and all other reagent used were of analytical grade.

Preparation ofMatrices

Nine formulations of Diltiazem hydrochloride employed for investigations containing

different ratios of HPMC of different grades were prepared by direct compression and coded

C1, C2, C3, D1, D2, D3, E1, E2 and E3. Similarly nine formulations of Atenolol containing

the same grades of HPMC were prepared and coded F1, F2, F3, G1, G2, G3, H1, H2, and H3.

The ratios of different grades of HPMC employed are shown in Table.[1] The amount of drug,

magnesium stearate, MCC and talc were kept constant while dicalcium phosphate was taken

in sufficient quantity to maintain a constant tablet weight of 120 mg. All the products and

process variables (other than the concentrations of two polymers) like mixing time,

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www.wjpr.net Vol 6, Issue 14, 2017. 1194 Matrix Swelling and Water Uptake Studies

Swelling was evaluated by weight. The matrices were placed in 900 ml dissolution medium

pH 6.3, at 370C. At different time intervals, the previously weighed tablets were removed,

gently wiped with a tissue to remove surface water, and reweighed. The percent water uptake

i.e., degree of swelling due to absorbed test liquid, can be estimated at regular time intervals

using the following equation –

% water Uptake = (Ws-Wi)/Wp *100

Where, Ws = Wt. of the swollen matrix at time t, Wi = Initial wt. of the matrix, Wp = wt. of

the polymer in the matrix. The polymer swelling or water uptake are mean of three

determinations.

The degree of swelling can be calculated by the following formula –

Degree of swelling = Ws-Wd/Wd*100

Where, Wd = Final dry wt. of the matrix, Ws = Swollen wt. of the same matrix at immersion

time (t). The swelling degree is the mean of at least three determinations.

The weight of the polymer in the matrix (Wp) and final dry weight of the matrix (Wd) are

shown in Table.[2]

Dissolution Studies

Dissolution studies were carried out for all the eighteen formulations in triplicate, employing

dissolution apparatus, using distilled water pH 6.3 as the dissolution medium at 50 rpm and

37  0.50C. An aliquot of sample was periodically withdrawn at suitable time intervals and

volume replaced with equivalent amounts of plain dissolution medium. The diltiazem

hydrochloride drug samples were analyzed at 237 nm. and the Atenolol drug samples were

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www.wjpr.net Vol 6, Issue 14, 2017. 1195 Table 1: Different ratios employed in formulations containing combinations of same HPMC grades.

Formulation Code HPMCK4M HPMCK100M DILTIAZEM HCL

C1 1 1 1

C2 2 2 1

C3 3 3 1

Formulation Code HPMCK4M HPMCK15M DILTIAZEM HCL

D1 1 1 1

D2 2 2 1

D3 3 3 1

Formulation Code HPMCK15M HPMCK100M DILTIAZEM HCL

E1 1 1 1

E2 2 2 1

E3 3 3 1

Formulation Code HPMCK15M HPMCK100M ATENOLOL

F1 1 1 1

F2 2 2 1

F3 3 3 1

G1 1 1 1

G2 2 2 1

G3 3 3 1

H1 1 1 1

H2 2 2 1

H3 3 3 1

Table 2: Final dry weight and weight of polymer in matrix tablets of different Formulations.

Formulation Code

Final Dry weight (Wd) (mg)

Weight of polymer in matrix (Wp) (mg)

C1 120 24

C2 127 48

C3 126 72

D1 124 24

D2 120 48

D3 125 72

E1 122 24

E2 125 48

E3 120 72

F1 120 24

F2 127 48

F3 126 72

G1 124 24

G2 122 48

G3 125 72

H1 122 24

H2 125 48

[image:4.595.85.496.93.443.2] [image:4.595.120.474.488.773.2]

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www.wjpr.net Vol 6, Issue 14, 2017. 1196 RESULTS AND DISCUSSION

The percent water uptake as a function of time for formulations containing diltiazemh

hydrochloride is reported in Table [3] Similarly Table [4] shows the result of formulations

containing atenolol drug matrices of different codes. The degree of swelling as a function of

time for formulations containing diltiazemh hydrochloride is reported in Table [5]. Similarly

Table [6] shows the degree of swelling result of formulations containing atenolol drug

matrices of different codes. The results of swelling studies are shown graphically for different

formulations. Fig1a shows the plot for water uptake as a function of time for formulation

codes C1, C2, C3, F1, F2 and F3 containing HPMC K4M and K100M combinations with

different ratios and Fig1b shows plot for degree of swelling as a function of time for

formulation codes C1, C2, C3, F1, F2, and F3. Similar plots are shown in Fig 2a and Fig 2b

for formulation codes D1, D2, D3, G1, G2, and G3 containing HPMC K4M and K15M

combinations with different ratios and Fig 3a and Fig 3b for formulation codes E1, E2, E3,

H1, H2, and H3 containing HPMC K15M and K100M combinations with different ratios.

The dissolution parameters of varied formulation with different ratios of polymer

combinations obtained during studies are shown in Table [7].

Table 3: Percent Water Uptake as a Function of Time for Formulations Containing

Diltiazem Hcl Drug.

Time Hrs. C1 C2 C3 D1 D2 D3 E1 E2 E3

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www.wjpr.net Vol 6, Issue 14, 2017. 1197 Table 4: Percent Water Uptake As A Function Of Time For Formulations Containing

Atenolol Drug.

Time Hrs. F1 F2 F3 G1 G2 G3 H1 H2 H3

0.5 83.33 33.33 45.83 58.33 37.50 41.67 125.00 72.92 69.44 1 175.00 95.83 81.94 87.50 77.08 55.56 170.83 112.50 97.22 2 433.33 220.83 168.06 379.17 218.75 176.39 325.00 229.17 206.94 3 558.33 285.42 215.28 441.67 291.67 201.39 487.50 322.92 256.94 4 683.33 343.75 256.94 587.50 335.42 250.00 708.33 366.67 312.50 5 800.00 443.75 315.28 658.33 410.42 284.72 762.50 445.83 333.33 6 895.83 485.42 347.22 837.50 452.08 309.72 904.17 493.75 361.11 8 1004.17 541.67 419.44 900.00 487.50 370.83 1025.00 556.25 444.44 10 1175.00 641.67 505.56 1025.00 602.08 437.50 1125.00 656.25 555.56 12 1291.67 756.25 588.89 1212.50 725.00 513.89 1320.83 822.92 595.83

Table 5: Degree of Swelling as a Function of Time for Formulations Containing

Diltiazem Hcl Drug.

Time Hrs. C1 C2 C3 D1 D2 D3 E1 E2 E3

0.5 18.33 15.75 28.57 22.50 15.75 28.57 27.05 30.4 44.17 1 37.50 37.80 49.21 45.83 37.80 49.21 37.70 44 60.83 2 89.17 85.04 98.41 95.83 85.04 98.41 66.39 90.4 126.67 3 114.17 110.24 126.19 122.50 110.24 126.19 98.36 128 156.67 4 139.17 132.28 150.00 145.83 132.28 150.00 140.16 144 190.00 5 162.50 170.08 185.71 185.83 170.08 185.71 152.46 173.6 203.33 6 181.67 187.40 201.59 204.17 187.40 201.59 180.33 192 220.83 8 204.17 207.09 245.24 225.00 207.09 245.24 204.10 218.4 270.83 10 238.33 246.46 295.24 266.67 246.46 295.24 223.77 256 337.50 12 262.50 292.13 344.44 315.00 292.13 344.44 262.30 320 354.17

Table 6: Degree of Swelling as a Function of Time for Formulations Containing

Atenolol Drug.

Time Hrs. F1 F2 F3 G1 G2 G3 H1 H2 H3

0.5 16.67 12.60 26.19 15.00 10.24 23.02 24.59 28 41.67 1 35.00 36.22 46.83 20.83 25.20 30.95 33.61 43.2 58.33 2 86.67 83.46 96.03 79.17 78.74 100.00 63.93 88 124.17 3 111.67 107.87 123.02 91.67 106.30 114.29 95.90 124 154.17 4 136.67 129.92 146.83 120.83 122.83 142.06 139.34 140.8 187.50 5 160.00 167.72 180.16 135.00 151.18 161.90 150.00 171.2 200.00 6 179.17 183.46 198.41 170.83 166.93 176.19 177.87 189.6 216.67 8 200.83 204.72 239.68 183.33 180.31 211.11 201.64 213.6 266.67 10 235.00 242.52 288.89 208.33 223.62 249.21 221.31 252 333.33 12 258.33 285.83 336.51 245.83 270.08 292.86 259.84 316 357.50

In this investigation it has been demonstrated that an inverse relationship exists between the

drug release rate and matrix-swelling rate. When the amount of HPMC in the matrix is high,

[image:6.595.61.541.326.487.2]

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irrespective of different grades causes a greater degree of swelling. This in turn reduces the

drug release, as the diffusional path length of drug is now longer. Conversely, reduction in

the amount of HPMC reduces the degree of swelling and the thickness of gel layer and thus

enables faster drug release. It is also demonstrated that HPMC of higher viscosity grades

swells to greater extent and has greater intrinsic water uptake property than that of the lower

viscosity grades. Also it is investigated that in both the drugs the same polymer combinations

shows the similar pattern of drug release.

Table 7: Dissolution Parameters of Different Formulations.

Formulation Code

Release at 12

hr. N

Degree of Swelling (%)

Percent of water uptake

C1 97.14 0.512 262.5 1312.5

C2 84.87 0.461 292.13 772.50

C3 75.6 0.452 344.44 602.78

D1 104.6 0.559 315.00 1237.5

D2 103.33 0.555 292.13 735.42

D3 86.6 0.467 344.44 527.78

E1 93.65 0.516 262.30 1333.33

E2 75.59 0.452 320.00 833.33

E3 64.1 0.439 354.17 590.28

F1 96.14 0.502 258.33 1291.67

F2 83.86 0.451 285.83 756.25

F3 74.5 0.442 336.51 588.89

G1 103.5 0.548 245.83 1212.50

G2 102.2 0.545 270.08 725.00

G3 85.5 0.456 292.86 513.89

H1 93.6 0.506 259.84 1320.83

H2 74.6 0.442 316 822.92

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www.wjpr.net Vol 6, Issue 14, 2017. 1200 CONCLUSION

Swelling studies reveals an inverse relationship between swelling effect and drug release

pattern from both the drugs matrices using the same polymer combinations. Comparison

studies shows almost similar swelling effect and drug release pattern from matrices

containing different drugs and same polymer combinations. Further, the rational combination

of different grades of polymer can be used satisfactorily to regulate the release of different

drugs in such matrices.

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